Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation

Milani, Emanuela S.; Brinkhaus, Heike; Dueggeli, Regula; Klebba, Ina; Mueller, Urs; Stadler, Michael; Kohler, Hubertus; Smalley, Matthew J.; Bentires‐Alj, Mohamed

doi:10.1242/dev.082941

Cited by 9 publications

(8 citation statements)

References 55 publications

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“…The PTP1B had been shown to be an oncogene in several studies [9,18,[31][32][33][34]; however, there is still averse evidence to blur this concept [35]. Consequently, the PTP1B expression patterns in BC were first confirmed in the current study using the ONCOMINE database prior to intense investigation.…”

Section: Overexpression Of Ptp1b In Bc Tissuesmentioning

confidence: 63%

PTP1B markedly promotes breast cancer progression and is regulated by miR‐193a‐3p

Liu

et al. 2018

The FEBS Journal

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The protein tyrosine phosphatase PTP1B, which is encoded by PTPN1, is a ubiquitously expressed nonreceptor protein tyrosine phosphatase. PTP1B has long been known to negatively regulate insulin and leptin receptor signalling. Recently, it was reported to be aberrantly expressed in cancer cells and to function as an important oncogene. In this study, we found that PTP1B protein levels are dramatically increased in breast cancer (BC) tissues and that PTP1B promotes the proliferation, and suppresses the apoptosis, of both HER2‐positive and triple‐negative BC cell lines. Bioinformatics analysis identified that the miRNA, miR‐193a‐3p, might potentially target PTP1B. We demonstrate that miR‐193a‐3p regulates PTP1B in BC cells and that it regulates the proliferation and apoptosis of BC cells by targeting PTP1B, both in vitro and in vivo. In conclusion, this study confirms that PTP1B acts as an oncogene in BC and demonstrates that miR‐193a‐3p can serve as a tumour suppressor gene in BC by targeting PTP1B.

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Section: Overexpression Of Ptp1b In Bc Tissuesmentioning

confidence: 63%

PTP1B markedly promotes breast cancer progression and is regulated by miR‐193a‐3p

Liu

et al. 2018

The FEBS Journal

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“…Genetic experiments have identified several inhibitors of STAT5 in the mammary gland including Caveolin-1, SOCS1, and PTP1B (Lindeman et al, 2001; Milani et al, 2012; Sotgia et al, 2006). Interestingly, Myc, when activated during a specific 72 hour window during mid-pregnancy, downregulates Caveolin-1, prematurely activates STAT5, and causes precocious lactation and involution (Blakely et al, 2005).…”

Section: Mammary Gland Differentiationmentioning

confidence: 99%

STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

Haricharan

2014

Molecular and Cellular Endocrinology

103

111

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The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer.

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“…Precocious mammary epithelial differentiation has been observed upon loss of Caveolin-3 (Sotgia et al, 2009) or tyrosine phosphatase PTP1B (Milani et al, 2013), inappropriate activation of STAT5 (Dong et al, 2010; Vafaizadeh et al, 2010) or overexpression of ELF5 (Oakes et al, 2008). To determine whether deregulated expression of Cav3 and Elf5 in the absence of miR-193b could be causal to the observed biology, we tested their functional role in vitro (Figure 7).…”

Section: Resultsmentioning

confidence: 99%

The STAT5-regulated miR-193b locus restrains mammary stem and progenitor cell activity and alveolar differentiation

Yoo

Kang

Feuermann

et al. 2014

Developmental Biology

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The transcription factor STAT5 mediates prolactin signaling and controls functional development of mammary tissue during pregnancy. This study has identified the miR-193b locus, also encoding miRNAs 365-1 and 6365, as a STAT5 target in mammary epithelium. While the locus was characterized by active histone marks in mammary tissue, STAT5 binding and expression during pregnancy, it was silent in most non-mammary cells. Inactivation of the miR-193b locus in mice resulted in elevated mammary stem/progenitor cell activity as judged by limiting dilution transplantation experiments of primary mammary epithelial cells. Colonies formed by mutant cells were larger and contained more Ki-67 positive cells. Differentiation of mammary epithelium lacking the miR-193b locus was accelerated during puberty and pregnancy, which coincided with the loss of Cav3 and elevated levels of Elf5. Normal colony development was partially obtained upon ectopically expressing Cav3 or upon siRNA-mediated reduction of Elf5 in miR-193b-null primary mammary epithelial cells. This study reveals a previously unknown link between the mammary-defining transcription factor STAT5 and a microRNA cluster in controlling mammary epithelial differentiation and the activity of mammary stem and progenitor cells.

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Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation

Cited by 9 publications

References 55 publications

PTP1B markedly promotes breast cancer progression and is regulated by miR‐193a‐3p

PTP1B markedly promotes breast cancer progression and is regulated by miR‐193a‐3p

STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

The STAT5-regulated miR-193b locus restrains mammary stem and progenitor cell activity and alveolar differentiation

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